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Resumen Introduccion La discinesia ciliar primaria (DCP) es una enfermedad caracterizada por una alteracion en la estructura ciliar que impide el correcto aclaramiento de las secreciones respiratorias. Su diagnostico es complejo y se basa en una combinacion de tecnicas. El objetivo de este estudio fue disenar un panel de genes incluyendo todos los genes causantes conocidos y comprobar su utilidad diagnostica en una cohorte de pacientes espanoles. Metodos Estudio transversal multicentrico de pacientes con sospecha elevada de DCP, aplicando los criterios de la European Respiratory Society. Diseno de un panel de genes para secuenciacion masiva con la tecnologia de captura SeqCap EZ technology, incluyendo 44 genes relacionados con la DCP. Resultados Se incluyo a 79 pacientes de los que 53 presentaron un diagnostico de DCP confirmado o muy probable. La sensibilidad del panel de genes fue del 81,1% con una especificidad del 100%. Se encontraron variantes candidatas en alguno de los genes del panel en 43 de los pacientes con DCP, siendo 51,2% (22/43) homocigotos y 48,8% (21/43) heterocigotos compuestos. Los genes causales mas frecuentes fueron DNAH5 y CCDC39. Encontramos 52 variantes distintas, 36 no descritas previamente en la literatura. Conclusiones El diseno y la implementacion de un panel de genes a medida tiene un alto rendimiento diagnostico genetico de la DCP, lo que permite conocer mejor la afectacion causal de estos pacientes y sentar las bases para futuros abordajes terapeuticos.

Introduction Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients. Methods This was a multicenter cross-sectional study of patients with a high suspicion of PCD according to European Respiratory Society criteria. We designed a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD. Results We included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature. Conclusions The design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches.

[Background] Children's diffuse lung disease, also known as children's Interstitial Lung Diseases (chILD), are a heterogeneous group of rare diseases with relevant morbidity and mortality, which diagnosis and classification are very complex. Epidemiological data are scarce. The aim of this study was to analyse incidence and prevalence of chILD in Spain., [Methods] Multicentre observational prospective study in patients from 0 to 18 years of age with chILD to analyse its incidence and prevalence in Spain, based on data reported in 2018 and 2019., [Results] A total of 381 cases with chILD were notified from 51 paediatric pulmonology units all over Spain, covering the 91.7% of the paediatric population. The average incidence of chILD was 8.18 (CI 95% 6.28–10.48) new cases/million of children per year. The average prevalence of chILD was 46.53 (CI 95% 41.81–51.62) cases/million of children. The age group with the highest prevalence were children under 1 year of age. Different types of disorders were seen in children 2–18 years of age compared with children 0–2 years of age. Most frequent cases were: primary pulmonary interstitial glycogenosis in neonates (17/65), neuroendocrine cell hyperplasia of infancy in infants from 1 to 12 months (44/144), idiopathic pulmonary haemosiderosis in children from 1 to 5 years old (13/74), hypersensitivity pneumonitis in children from 5 to 10 years old (9/51), and scleroderma in older than 10 years old (8/47)., [Conclusions] We found a higher incidence and prevalence of chILD than previously described probably due to greater understanding and increased clinician awareness of these rare diseases., [Antecedentes] Las neumopatías intersticiales pediátricas, también conocidas con el acrónimo chILD (del inglés children's Interstitial Lung Diseases), es un grupo heterogéneo de enfermedades raras con morbimortalidad relevante, cuyo diagnóstico y clasificación son complejos. Los estudios epidemiológicos son escasos. El objetivo de este trabajo fue analizar la incidencia y la prevalencia de chILD en España., [Métodos] Estudio prospectivo observacional multicéntrico en pacientes de 0 a 18 años afectos de chILD para analizar la incidencia y la prevalencia en España, a partir de datos recogidos en 2018 y 2019., [Resultados] Se recogieron 381 casos de chILD entre 51 unidades de neumología pediátrica de toda España, que cubrían el 91,7% de la población pediátrica. La incidencia promedio fue 8,18 (IC 95%: 6,28-10,48) casos nuevos/millón de niños por año. La prevalencia promedio fue de 46,53 (IC 95%: 41,81-51,62) casos/millón de niños. El grupo de edad con mayor prevalencia fue el de niños menores de un año. Se observaron diferentes entidades en niños de 2 a 18 años en comparación con niños de 0 a 2 años. Los diagnósticos más frecuentes fueron: glucogenosis intersticial pulmonar primaria en neonatos (17/65), hiperplasia de células neuroendocrinas en lactantes de uno a 12 meses (44/144), hemosiderosis pulmonar idiopática en niños de uno a 5 años (13/74), neumonía por hipersensibilidad en niños de 5 a 10 años (9/51) y esclerodermia en mayores de 10 años (8/47)., [Conclusiones] Encontramos una mayor incidencia y prevalencia de chILD que las descritas previamente, probablemente debido a un mayor conocimiento y detección de estas enfermedades raras., ATV was supported by a grant from the Spanish Society of Paediatric Pulmonology and a Short Term Scientific Mission of the Cost CA 16125 ENTeR-chILD. This work was supported by a grant from the Spanish Society of Pneumology and Thoracic Surgery (SEPAR 2017/492). AMG was supported by a grant from the project HCQ4Surfdefect, in E-Rare-3, the ERA-Net for Research on Rare Diseases (Acciones complementarias en Salud, Instituto Carlos III, Madrid, Spain, AC16/00027) and Cost CA 16125 ENTeR-chILD.

Introduction It remains unclear if prematurity itself can influence post delivery lung development and particularly, the bronchial size. Aim To assess lung function during the first two years of life in healthy preterm infants and compare the measurements to those obtained in healthy term infants during the same time period. Methods This observational longitudinal study assessed lung function in 74 preterm (30 + 0 to 35 + 6 weeks’ gestational age) and 76 healthy term control infants who were recruited between 2011 and 2013. Measurements of tidal breathing, passive respiratory mechanics, tidal and raised volume forced expirations (V’maxFRC and FEF25–75, respectively) were undertaken following administration of oral chloral hydrate sedation according to ATS/ERS recommendations at 6- and 18-months corrected age. Results Lung function measurements were obtained from the preterm infants and full term controls initially at 6 months of age. Preterm infants had lower absolute and adjusted values (for gestational age, postnatal age, sex, body size, and confounding factors) for respiratory compliance and V’maxFRC. At 18 months corrected postnatal age, similar measurements were repeated in 57 preterm infants and 61 term controls. A catch-up in tidal volume, respiratory mechanics parameters, FEV0.5 and forced expiratory flows was seen in preterm infants. Conclusion When compared with term controls, the lower forced expiratory flows observed in the healthy preterm group at 6 months was no longer evident at 18 months corrected age, suggesting a catch-up growth of airway function.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is characterized by an alteration in the ciliary structure causing difficulty in the clearance of respiratory secretions. Diagnosis is complex and based on a combination of techniques. The objective of this study was to design a gene panel including all known causative genes, and to corroborate their diagnostic utility in a cohort of Spanish patients.; METHODS: This was a multicenter cross-sectional study of patients with a high suspicion of PCD, according to European Respiratory Society criteria, designed around a gene panel for massive sequencing using SeqCap EZ capture technology that included 44 genes associated with PCD.; RESULTS: We included 79 patients, 53 of whom had a diagnosis of confirmed or highly probable PCD. The sensitivity of the gene panel was 81.1%, with a specificity of 100%. Candidate variants were found in some of the genes of the panel in 43 patients with PCD, 51.2% (22/43) of whom were homozygotes and 48.8% (21/43) compound heterozygotes. The most common causative genes were DNAH5 and CCDC39. We found 52 different variants, 36 of which were not previously described in the literature.; CONCLUSIONS: The design and implementation of a tailored gene panel produces a high yield in the genetic diagnosis of PCD. This panel provides a better understanding of the causative factors involved in these patients and lays down the groundwork for future therapeutic approaches. Copyright © 2020 SEPAR. Publicado por Elsevier Espana, S.L.U. All rights reserved.

Objective Long‐term respiratory consequences of bronchopulmonary dysplasia (BPD) in preterm infants born in the post‐surfactant era (“new” BPD) remain partially unknown. The present study aimed to evaluate the respiratory outcomes of “new” BPD in adolescents who were born preterm. Methods This multicenter, cross‐sectional study included 286 adolescents born between 2003 and 2005 (mean age: 14.2 years); among them, 184 and 102 were born extremely preterm (EP

Resumen Introduccion La publicacion reciente de ecuaciones de referencia de espirometria multietnicas para edades de 3 a 95 anos tiene como objetivo evitar las discontinuidades relacionadas con la edad y proporcionar un estandar mundial para la interpretacion de los resultados de la espirometria. Objetivos Validar las ecuaciones de la Global Lung Function Initiative (GLI-2012) y All ages (FEV 0,5 ) en ninos preescolares espanoles, para verificar la adecuacion de estas ecuaciones para su uso clinico. Metodos Se realizaron espirometrias forzadas en ninos de 3 a 6 anos de edad de 10 colegios seleccionados aleatoriamente en Barcelona (Espana). Se aplicaron los criterios de control de calidad de Stanojevic et al. Se calculo el z-score segun las ecuaciones GLI-2012. Se considero que para que las ecuaciones GLI-2012 pudieran ser aplicables en nuestra poblacion, la media expresada en z-score de cada parametro debia de tener un valor proximo a 0 y una desviacion estandar (DS) de 1, aceptando como maximo una diferencia de ± 0,5 z-scores respecto a la media. Resultados De los 543 ninos reclutados, 405 (74,6%) eran «sanos», y de ellos 380 caucasicos. De estos, 81,6% (169 mujeres, 141 hombres) realizaron maniobras tecnicamente aceptables y reproducibles para evaluar la FEVt, y el 69,5% logro una meseta espiratoria final adecuada. Los z-scores para FVC, FEV 1 , FEV 1 /FVC, FEV 0,75 , FEV 0,75 /FVC, FEV 0,5 , FEF 75 y FEF 25-75 estuvieron incluidos entre ± 0,5 z-scores, salvo el FEV 1 /FVC (0,53 z-scores). Conclusiones Las ecuaciones GLI son apropiadas para los ninos preescolares espanoles. Estos datos proporcionan nuevas evidencias para apoyar su utilizacion.

Introduction: Post-infectious bronchiolitis obliterans (PIBO) is a rare chronic obstructive lung disease secondary to small airway injury-related chronic inflammation. The aim of this study is to describe clinical features, lung function test results and outcomes of 62 children with PIBO. Methods: Sixty-two children diagnosed with PIBO at Hospital Universitari Vall d’Hebron in Barcelona (Spain) between 2010-2018 were retrospectively analysed. Their clinical characteristics, lung function test (spirometry, pletysmography, lung clearance index), treatment and outcomes were reported. Results: Mean follow up was 9 years. 48% were males with a median age at diagnosis 1.45 years (+/- 2.2). More than a half (64.5%) were admitted with a median stay of 4 days (+/- 8). 45% required oxygen supplementation although only 14.5% needed mechanical ventilation. Regarding initial infection, patients with positive microbial identification, Adenovirus was the most common. HRCT were consistent with the PIBO diagnosis in all of the patients. Initial spirometry revealed a fixed obstructive airway dysfunction and regarding plethysmographic variables were high. Lung clearance index (LCI) was done in 17 patients with mean values of 15,47, higher from the controlls described on literature. Most patients presented a good long-term outcome; only a small percentage had a severe disease with chronic respiratory failure, needing in lung transplantation 4 patients (6%), in all explants wit found bronchitis and bronchiolitis. Conclusions: Patients with chronic disease have good outcome in our follow up until 18 years of age.

Resumen: Introducción: La hipoplasia pulmonar es la anomalía congénita más frecuentemente asociada a mortalidad perinatal. Material y métodos: Se ha realizado un estudio descriptivo retrospectivo de los casos de hipoplasia pulmonar diagnosticados entre 1995 y 2014 en un hospital universitario de tercer nivel, analizando estudios prenatales, manifestaciones clínicas, pruebas diagnósticas, tratamiento, datos de seguimiento a largo plazo y supervivencia. Resultados: Se identificaron 60 casos, todos con estudio prenatal. Dieciséis recibieron intervención quirúrgica intraútero. La hernia diafragmática congénita fue la entidad más frecuentemente asociada. La manifestación clínica más habitual fue distrés respiratorio neonatal, hipoxemia grave y necesidad de soporte con ventilación mecánica. Se halló un 47% de mortalidad antes de los 60 días de vida y del 75% en las primeras 24 h de vida. Durante el seguimiento de los supervivientes se detectaron episodios de neumonías y bronquitis recidivantes, función pulmonar con patrón obstructivo y aceptable calidad de vida y tolerancia al ejercicio. Conclusiones: La elevada mortalidad neonatal y la importante morbilidad a largo plazo de la hipoplasia pulmonar requieren de un diagnóstico temprano y la intervención de un equipo multidisciplinar especializado. Abstract: Introduction: Pulmonary hypoplasia is the most frequent congenital anomaly associated with perinatal mortality. Material and methods: A retrospective and descriptive review was conducted on cases of patients diagnosed with pulmonary hypoplasia between 1995 and 2014 in a tertiary university hospital. An analysis was made of the prenatal imaging, clinical manifestations, post-natal diagnostic tests, treatment and management, long-term follow up, and survival data. Results: A total of 60 cases were identified, all of them with prenatal imaging. Sixteen patients required foetal surgery. Congenital diaphragmatic hernia was the most frequent diagnosis. Main clinical presentation was respiratory distress with severe hypoxemia and high requirements of mechanical ventilation. Mortality rate was 47% within first 60 days of life, and 75% for the first day of life. Pneumonia and recurrent bronchitis episodes were observed during follow-up. They had a lung function obstructive pattern, and their quality of life and exercise tolerance was good. Conclusions: High neonatal mortality and significant long-term morbidity associated with pulmonary hypoplasia requires an early diagnosis and a specialised multidisciplinary team management.

Background: Epidemiologic data suggest a role of low vitamin D levels in respiratory tract infections in infants. Objectives: To determine whether high dose (1,000 IU/d) vs standard dose vitamin D supplementation reduces the proportion of infants with acute bronchitis during the first year of life. Secondary outcomes were reduction of infants with recurrent bronchitis, hospitalizations for acute bronchiolitis and upper respiratory tract infections (URTI), and the achievement of a higher percentage of children with adequate vitamin D blood levels. Methods: Phase III multicentre randomized double blind clinical trial. Healthy full-term Infants were randomized to receive either 400 IU or 1,000 IU/d of vitamin D up to 1 year of age. Results: 198 children were included, 94 in the 400 IU group and 104 in the 1000 IU group. There were no differences in the percentage of children who presented acute bronchitis, recurrent bronchitis, URTI, or were admitted due to bronchiolitis. At birth, 72.7% of the children had severe or moderate vitamin D deficiency. A higher percentage of children achieved vitamin D levels > 30 ng/ml in the 1,000 IU/day group (75% vs 55.9%). The profile of adverse effects was similar in both groups. Conclusions: Although it was safe and resulted in higher vitamin D levels, daily administration of 1,000 IU of vitamin D, compared to 400 IU, did not decrease acute or recurrent bronchitis or URTI in infants. Supported by a grant from Spanish Ministry of Health (EC11-476)

Background: Subcutaneous treprostinil is recommended as add-on therapy in high-risk patients with pulmonary arterial hypertension (PAH), but there are few data on its use and outcome in children. Methods: Retrospective observational study. Medical records from paediatric patients diagnosed with PAH during the last 10 years were reviewed. We evaluated safety and outcome of patients treated with subcutaneous treprostinil. Results: We identified 10 patients (5 girls) with PAH who initiated treatment with treprostinil between 2011 and 2017: 6 with idiopathic PAH and 4 with PAH related to congenital heart disease. Median age at diagnosis was 1.8 years (0.1-7.8). All patients were in functional class III when they started treprostinil after a median of 3.3 years (0.3-11) since the diagnosis, and all were on oral combined therapy and inhaled iloprost. Treprostinil was gradually increased while iloprost was downtitrated. At 3 months: 5 patients improved and 5 stabilized; median reduction of brain-type natriuretic peptide levels was 83% (7/10 patients); all showed persistent right ventricle dysfunction with significant enlargement. Treprostinil median maximum dose was 68 ng/Kg/min (32-100), median duration was 11 months (2-26). Side effects included local pain, erythema and cellulitis (2/10), although well tolerated without stopping the treatment. Outcome: 4 continued on treprostinil and oral therapy, 2 transitioned to epoprostenol, 6 received a lung transplant (including 2 on epoprostenol). Two died due to post-transplant complications. Conclusions: Subcutaneous treprostinil can improve or stabilize high-risk PAH children with few side effects, being well accepted by them and their families.

Introduction Recent publication of multi-ethnic spirometry reference equations for subjects aged from 3 to 95 years aim to avoid age-related discontinuities and provide a worldwide standard for interpreting spirometric test results. Objectives To assess the agreement of the Global Lung Function Initiative (GLI-2012) and All ages (FEV0.5) reference equations with the Spanish preschool lung function data. To verify the appropriateness of these reference values for clinical use in Spanish preschool children. Methods Spirometric measurements were obtained from children aged 3–6 years attending 10 randomly selected schools in Barcelona (Spain). Stanojevic's quality control criteria were applied. z-Scores were calculated for the spirometry outcomes based on the GLI equations. If the z-score (mean) of each parameter was close to 0, with a maximum difference of ±0.5 from the mean and a standard deviation of 1, the GLI-2012 equations would be applicable in our population. Results Of 543 children recruited, 405 (74.6%) were ‘healthy’, and of these, 380 were Caucasians. Of these 380, 81.6% (169 females, 141 males) performed technically acceptable and reproducible maneuvers to assess FEVt, and 69.5% achieved a clear end-expiratory plateau. z-Scores for FVC, FEV1, FEV1/FVC, FEV0.75, FEV0.75/FVC, FEV0.5, FEF75 and FEF25–75 all fell within ±0.5, except for FEV1/FVC (0.53 z-scores). Conclusions GLI equations are appropriate for Spanish preschool children. These data provide further evidence to support widespread application of the GLI reference equations.

Summary Pulmonary hypertension (PH) in children is a serious disorder, for which the major goal of treatment is to prevent progressive vascular remodeling, and improve clinical status and survival. Iloprost is approved for the treatment of PH in adults; however, few studies have evaluated its effects in children. The objective of this study is to analyze the long-term effects of inhaled iloprost treatment in children with PH. A retrospective study was conducted in patients treated with iloprost between 2000 and 2012. Patients with left–right cardiac shunt and persistent PH of the newborn were excluded. The cohort comprised 22 patients (15 females) with a median age of 2.6 years. Twelve patients had pulmonary arterial hypertension including idiopathic (n = 6), hereditary (n = 2) and associated (congenital heart disease [n = 3], and schistosomiasis [n = 1]). One patient had pulmonary veno-occlusive disease, six patients had PH secondary to lung disease and three had multifactorial PH. Median mean pulmonary arterial pressure was 55 mmHg and median pulmonary vascular resistance was 15.5 Wood units. Good tolerability was observed, with the exception of one case of recurring abdominal pain. PH resolved in two patients, with functional capacity improvement in 10 patients and stabilization in three patients. The clinical condition of six patients deteriorated; two died, and two received lung transplants. In conclusion, the results of this uncontrolled study showed that iloprost was effective and well tolerated in children. However, further research is needed to support this study, as PH is a serious condition that can require organ transplantation or result in death. Pediatr Pulmonol. 2015; 50:370–379. © 2014 Wiley Periodicals, Inc.

Resumen Objetivo Valorar la hiperespuesta bronquial en ninos menores de 4 anos con bronquitis sibilantes de repeticion, y determinar si su presencia o ausencia permite predecir la evolucion posterior hacia un fenotipo de bronquitis sibilantes transitorias o persistentes. Poblacion y metodos Se realizo una prueba de broncoprovocacion con metacolina utilizando un metodo modificado de respiracion a volumen corriente, sin sedacion a un grupo de pacientes de 8 a 47 meses de edad, con bronquitis sibilantes recurrentes y a un grupo control de ninos sanos. Se valoro como respuesta positiva, la presencia de sibilantes, la disminucion de la saturacion de oxigeno ≥5% o el aumento de la frecuencia respiratoria >50% (PCwheeze [PCw]). Se realizo un seguimiento clinico posterior de los pacientes para valorar su evolucion. Resultados Se estudiaron 63 pacientes y 16 controles (edad media 23,9 vs. 25,2 meses). La PCw fue inferior a la del grupo control (≤4 mg/ml) en 43 ninos (68%) del grupo bronquitis (p Conclusiones Un porcentaje elevado de ninos menores de 4 anos afectos de bronquitis sibilantes presentaron hiperrespuesta bronquial. La evolucion posterior a un fenotipo de bronquitis sibilantes transitorias o persistentes no se relaciono con la hiperrespuesta bronquial.

Resumen Introduccion El objetivo del estudio ha sido valorar la inflamacion bronquial en ninos preescolares con bronquitis de repeticion, mediante la determinacion del oxido nitrico exhalado. Pacientes y metodos Se incluyo en el estudio a pacientes menores de 4 anos con antecedentes de 3 episodios de sibilantes en el ultimo ano (n=63), asi como un grupo control (n=30). Se determino el oxido nitrico exhalado mediante la tecnica de recogida off-line , con respiracion espontanea a volumen corriente con mascarilla, recogida en bolsa de Mylar. Resultados El grupo con bronquitis presento como media una fraccion de oxido nitrico en aire exhalado (FE NO ) mas elevada (media±desviacion estandar: 5,3±1,3 ppb) que el grupo control (4,6±1,1) (p=0,02). Hubo una diferencia significativa (p 400/μl) presentaban concentraciones de FE NO mas altas (p NO y el hecho de tener una prueba de provocacion bronquial positiva a la metacolina. Se realizo un seguimiento de los pacientes durante mas de 20 meses. No hubo diferencias significativas (p=0,36) en el valor inicial de la FE NO entre los pacientes que posteriormente presentaron sibilancias transitorias (5,2±0,98 ppb), infrecuentes (5,6±1,5 ppb) o frecuentes (4,8±1,34 ppb). Conclusiones Los ninos menores de 4 anos afectados de bronquitis sibilantes de repeticion en fase asintomatica presentan una discreta elevacion de la FE NO , con una amplia superposicion de valores con el grupo control.

Objetivo Valorar la seguridad del metodo de la auscultacion traqueal para medir la hiperrespuesta bronquial en ninos sanos menores de 4 anos de edad, sin sedacion, y establecer valores de normalidad. Poblacion y metodos Se incluyo en el estudio a ninos sanos de entre 6 meses y 4 anos de edad. Se les realizo una prueba de provocacion bronquial con metacolina mediante la tecnica de la respiracion a volumen corriente, en ninos no sedados, utilizando un protocolo acortado. Se considero positiva la prueba cuando se auscultaron sibilantes en la traquea, la saturacion arterial de oxigeno (SaO2) disminuyo un 5% o mas, o bien aumento la frecuencia respiratoria un 50% o mas. Resultados Se estudio a 16 ninos de 8 a 47 meses de edad (mediana: 23,5 meses; desviacion estandar: 12,2 meses). En 11 ninos no hubo respuesta a la metacolina, y en 5 la respuesta fue positiva a la concentracion de 8 mg/ml. La prueba se considero positiva en 3 casos por la auscultacion de sibilancias traqueales, en uno por la auscultacion de sibi-lancias y descenso de la SaO2, y en otro por un descenso de la SaO2del 5% o superior. En ningun caso la SaO2 disminuyo por debajo del 93%. Conclusiones El metodo de la auscultacion traqueal es sencillo, adecuado y seguro para valorar la presencia de hiperrespuesta bronquial en ninos menores de 4 anos de edad, sin necesidad de sedarlos. La concentracion minima a la que los ninos sanos de esta edad responden a la metacolina es 8 mg/ml.

OBJECTIVE: To assess the safety of the tracheal auscultation method for measuring bronchial hyperresponsiveness in healthy unsedated children aged less than 4 years and to establish a range of normal bronchial hyperresponsiveness values. POPULATION AND METHODS: The study population consisted of healthy children aged between 6 months and 4 years. A methacholine bronchial provocation test was administered to unsedated children, using the tidal volume breathing technique and applying an abbreviated protocol. The test was considered positive when wheezing was heard in the trachea, arterial oxygen saturation (SaO2) fell by 5% or more, or respiratory rate increased by 50% or more. RESULTS: A total of 16 children were studied. Ages ranged from 8 to 47 months, with a mean (SD) of 23.5 (12.2) months. There was no response to the methacholine in 11 children. In the other 5 children, there was a positive response at a concentration of 8 mg/mL. Response to the test was considered positive on the basis of tracheal wheezing in 3 cases, tracheal wheezing and a fall in SaO2 in 1 case, and a fall of more than 5% in SaO2 in 1 case. SaO2 never fell below 93%. CONCLUSIONS: As a means for assessing bronchial hyperresponsiveness, the tracheal auscultation method is appropriate, is simple to apply, and can be safely administered to unsedated children aged less than 4 years. The lowest concentration at which a response to methacholine occurs in healthy children of this age group is 8 mg/mL.

Introduction: Pulmonary hypoplasia is the most frequent congenital anomaly associated with perinatal mortality. Material and methods: A retrospective and descriptive review was conducted on cases of patients diagnosed with pulmonary hypoplasia between 1995 and 2014 in a tertiary university hospital. An analysis was made of the prenatal imaging, clinical manifestations, post-natal diagnostic tests, treatment and management, long-term follow up, and survival data. Results: A total of 60 cases were identified, all of them with prenatal imaging. Sixteen patients required foetal surgery. Congenital diaphragmatic hernia was the most frequent diagnosis. Main clinical presentation was respiratory distress with severe hypoxaemia and high requirements of mechanical ventilation. Mortality rate was 47% within first 60 days of life, and 75% for the first day of life. Pneumonia and recurrent bronchitis episodes were observed during follow-up. They had a lung function obstructive pattern, and their quality of life and exercise tolerance was good. Conclusions: High neonatal mortality and significant long-term morbidity associated with pulmonary hypoplasia requires an early diagnosis and a specialised multidisciplinary team management. Resumen: Introducción: La hipoplasia pulmonar es la anomalía congénita más frecuentemente asociada a mortalidad perinatal. Material y métodos: Se ha realizado un estudio descriptivo retrospectivo de los casos de hipoplasia pulmonar diagnosticados entre 1995 y 2014 en un hospital universitario de tercer nivel, analizando estudios prenatales, manifestaciones clínicas, pruebas diagnósticas, tratamiento, datos de seguimiento a largo plazo y supervivencia. Resultados: Se identificaron 60 casos, todos con estudio prenatal. Dieciséis recibieron intervención quirúrgica intraútero. La hernia diafragmática congénita fue la entidad más frecuentemente asociada. La manifestación clínica más habitual fue distrés respiratorio neonatal, hipoxemia grave y necesidad de soporte con ventilación mecánica. Se halló un 47% de mortalidad antes de los 60 días de vida y del 75% en las primeras 24 h de vida. Durante el seguimiento de los supervivientes se detectaron episodios de neumonías y bronquitis recidivantes, función pulmonar con patrón obstructivo y aceptable calidad de vida y tolerancia al ejercicio. Conclusiones: La elevada mortalidad neonatal y la importante morbilidad a largo plazo de la hipoplasia pulmonar requieren de un diagnóstico temprano y la intervención de un equipo multidisciplinar especializado.

Pulmonary hypertension (PH) in children is a serious disorder, for which the major goal of treatment is to prevent progressive vascular remodeling, and improve clinical status and survival. Iloprost is approved for the treatment of PH in adults; however, few studies have evaluated its effects in children. The objective of this study is to analyze the long-term effects of inhaled iloprost treatment in children with PH. A retrospective study was conducted in patients treated with iloprost between 2000 and 2012. Patients with left-right cardiac shunt and persistent PH of the newborn were excluded. The cohort comprised 22 patients (15 females) with a median age of 2.6 years. Twelve patients had pulmonary arterial hypertension including idiopathic (n = 6), hereditary (n = 2) and associated (congenital heart disease [n = 3], and schistosomiasis [n = 1]). One patient had pulmonary veno-occlusive disease, six patients had PH secondary to lung disease and three had multifactorial PH. Median mean pulmonary arterial pressure was 55 mmHg and median pulmonary vascular resistance was 15.5 Wood units. Good tolerability was observed, with the exception of one case of recurring abdominal pain. PH resolved in two patients, with functional capacity improvement in 10 patients and stabilization in three patients. The clinical condition of six patients deteriorated; two died, and two received lung transplants. In conclusion, the results of this uncontrolled study showed that iloprost was effective and well tolerated in children. However, further research is needed to support this study, as PH is a serious condition that can require organ transplantation or result in death.

To evaluate bronchial hyperresponsiveness in children under 4 years of age with recurrent wheezing bronchitis, and to determine if its presence or absence can predict the subsequent progression to a transient or persistent wheezing bronchitis phenotype.A bronchial challenge test was performed with methacholine using a modified tidal volume method, without sedation in a group of patients from 8 to 47 months of age with recurrent wheezing bronchitis and a control group of healthy children. A decrease in oxygen saturation of ≥ 5% or an increase in respiration rate of50% [PCwheeze (PCw)] was considered a positive response. The patients were subsequently clinically followed up to assess their progress.A total of 63 patients and 16 controls were studied (mean age 23.9 vs. 25.2 months). The PCw was lower than the control group (≤ 4 mg/ml) in 43 (68%) children from the bronchitis group (P0.001). No significant adverse effects were observed on performing the test. After a mean follow up of 28.5 months, completed in 49 of the patients, no differences were seen between the presence of bronchial hyperresponsiveness at the beginning of the study and the subsequent progression to transient, infrequent and frequent wheezing (P=0.63).A high percentage of children under 4 years of age affected by wheezing bronchitis had a bronchial hyperresponse. The subsequent progression to transient or persistent wheezing bronchitis phenotype is not associated with bronchial hyperresponsiveness.

The objective of the study was to assess bronchial inflammation in preschool children with recurrent bronchitis by measuring exhaled nitric oxide.The study included patients under 4 years of age with at least 3 episodes of wheezing in the past year (n=63) and a control group (n=30). Exhaled nitric oxide was measured in samples collected offline during spontaneous tidal breathing with a face mask and stored in Mylar balloons.The fractional exhaled nitric oxide concentration (FE(NO)) was higher in the group with bronchitis (mean [SD], 5.3 [1.3] parts per billion [ppb]) than in the control group (4.6 [1.1]ppb) (P=.02). There was a significant difference between the control group and children in the bronchitis group not treated with inhaled corticosteroids (P.05), but not between controls and corticosteroid-treated patients. A relationship with eosinophil count was observed in that those with higher counts (400 microL) had higher FE(NO) levels (P.01). No relationship was observed between FE(NO) and a positive methacholine challenge test. Follow-up lasted at least 20 months. The initial FE(NO) level did not differ significantly according to whether patients were subsequently transient, infrequent, or frequent wheezers (5.2 [0.98]ppb, 5.6 [1.5]ppb, and 4.8 [1.34]ppb, respectively; P=.36).In children under 4 years of age with recurrent wheezing bronchitis who were asymptomatic at study entry, a small increase in FE(NO) was observed although there was a good deal of overlap with the control group.